You may have heard the military rule for the summoning of troops to a battlefield: “March to the sound of the guns.” In science the opposite is the one for you, as expressed in Principle Number Three:
March away from the sound of the guns. Observe the fray from a distance, and while you are at it, consider making your own fray.
Once you have settled upon a subject you can love, your potential to succeed will be greatly enhanced if you study it enough to become a world-class expert. This goal is not as difficult as it may seem, even for a graduate student. It is not overly ambitious. There are thousands of subjects in science, sprinkled through physics and chemistry, biology and the social sciences, where it is possible in a short time to attain the status of an authority. If the subject is still thinly populated, you can with diligence and hard work even become the world authority at a young age. Society needs this level of expertise, and it rewards the kind of people willing to acquire it.
The already existing information, and what you yourself will discover, may at first be skimpy and difficult to connect to other bodies of knowledge. If this proves to be the case, that’s very good. Why should the path to a scientific frontier usually be hard rather than easy? The answer is stated as Principle Number Four:
In the search for scientific discoveries, every problem is an opportunity. The more difficult the problem, the greater the likely importance of its solution.
The truth of this guidebook dictum can be most clearly seen in extreme cases. The sequencing of the human genome, the search for life on Mars, and the finding of the Higgs boson were each of profound importance for medicine, biology, and physics, respectively. Each required the work of thousands, and cost billions. Each was worth all the trouble and expense. But on a far smaller scale, in fields and subjects less advanced, a small squad of researchers, even a single individual, can with effort devise an important experiment at relatively low cost.
This brings me to the ways in which scientific problems are found and discoveries made. Scientists, mathematicians among them, follow one of two pathways. First, early in the research a problem is identified, and then a solution is sought. The problem may be relatively small (for example, what is the average life span of a Nile crocodile?) or large (what is the role of dark matter in the universe?). As an answer emerges, other phenomena are typically discovered, and other questions raised. The second strategy is to study a subject broadly, while searching for any previously unknown or even unimagined phenomena. The two strategies of original scientific research are stated as Principle Number Five:
For every problem in a given discipline of science, there exists a species or other entity or phenomenon ideal for its solution. (Example: a kind of mollusk, the sea hare Aplysia, proved ideal for exploring the cellular base of memory.)
Conversely, for every species or other entity or phenomenon, there exist important problems for the solution of which it is ideally suited. (Example: bats were logical for the discovery of sonar.)
Obviously, both strategies can be followed, together or in sequence, but by and large scientists who use the first strategy are instinctive problem solvers. They are prone by taste and talent to select a particular kind of organism, or chemical compound, or elementary particle, or physical process, to answer questions about its properties and roles in nature. Such is the predominant research activity in the physical sciences and molecular biology.
The following example is a fictitious scenario of the first strategy, but, I promise you, is close to true dramas that occur in laboratories:
Think of a small group of white-coated men and women in a laboratory—early one afternoon, let us say—watching the readout on a digital monitor. That morning, before setting up the experiment, they were in a nearby conference room, conferring, occasionally taking turns at the blackboard to make an argument. With coffee break, lunch, a few jokes, they decide to try this or that. If the data in the readout are as expected, that will be very interesting, a real lead. “It would be what we’re looking for,” the team leader says. And it is! The object of the search is the role of a new hormone in the mammalian body. First, though, the team leader says, “Let’s break out some champagne. Tonight, we’ll all have dinner at a decent restaurant and start talking about what comes next.”
In biology, the first, problem-oriented strategy (for every problem, an ideal organism) has resulted in a heavy emphasis on several dozen “model species.” When in your studies you take up the molecular basis of heredity you will learn a great deal that came from a bacterium living in the human gut, E. coli (condensed from its full scientific name, Escherichia coli). For the organization of cells in the nervous system, there is inspiration from the roundworm C. elegans (Caenorhabditis elegans). And for genetics and embryonic development, you will become familiar with fruitflies of the iconic genus Drosophila. This is, of course, as it should be. Better to know one thing in depth rather than a dozen things at their surface only.
Still, keep in mind that during the next few decades there will be at most only a few hundred model species, out of close to two million other species known to science by scarcely more than a brief diagnosis and a Latinized name. Although the latter multitude tend to possess most of the same basic processes discovered in the model species, they further display among them an immense array of idiosyncratic traits in anatomy, physiology, and behavior. Think, in one sweep of your mind, first of a smallpox virus, then of all you know about it. Then the same for an amoeba, and then on to a maple tree, blue whale, monarch butterfly, tiger shark, and human being. The point is that each such species is a world unto itself, with a unique biology and place in an ecosystem, and, not least, an evolutionary history thousands to millions of years old.
When a biologist studies a group of species, ranging anywhere from, say, elephants with three living species to ants with fourteen thousand species, he or she typically aims to learn everything possible over a wide range of biological phenomena. Most researchers working this way, following the second strategy of research, are properly called scientific naturalists. They love the organisms they study for their own sake. They enjoy studying creatures in the field, under natural conditions. They will tell you, correctly, that there is infinite detail and beauty even in those that people at first find least attractive—slime molds, for example, dung beetles, cobweb spiders, and pit vipers. Their joy is in finding something new, the more surprising the better. They are the ecologists, taxonomists, and biogeographers. Here is a scenario of a kind I have personally experienced many times:
Think of two biologists hunting in a rain forest, packing heavy collecting equipment, with an online field guide waiting back at camp and DNA analysis at the home laboratory. “Good God, what is that?” one says, pointing to a small, strangely shaped, brilliantly colored animal plastered onto the underside of a palm leaf. “I think it’s a hylid frog,” his companion replies. “No, no, wait, I’ve never seen anything like it. It’s got to be something new. What the hell is it? Listen, get close, and be careful, don’t lose it. There, got it. We’re not going to preserve it yet. You never know, it might be an endangered species. Let’s take it back alive to camp and see what we can find on the Encyclopedia of Life website. There’s that guy at Cornell, he knows all the amphibians like this one pretty well, I think. We might check in with him. First, though, we ought to look around for more specimens, get all the information we can.” The pair arrive back at camp and start pulling up information. What they find is astonishing. The frog appears to be a new genus, unrelated to any other previously known. Scarcely believing, the pair go online to spread news of the discovery to other specialists around the world.
The potential paths you can follow with a scientific career are vast in number. Your choice may take you into one of the scenarios I’ve described, or not. The subject for you, as in any true love, is one in which you are interested and that stirs passion and promises pleasure from a lifetime of devotion.
II
THE
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PROCESS
Charles Darwin at 31 years of age. Modified from painting by George Richmond.
Four
WHAT IS SCIENCE?
WHAT IS THIS grand enterprise called science that has lit up heaven and earth and empowered humanity? It is organized, testable knowledge of the real world, of everything around us as well as ourselves, as opposed to the endlessly varied beliefs people hold from myth and superstition. It is the combination of physical and mental operations that have become increasingly the habit of educated peoples, a culture of illuminations dedicated to the most effective way ever conceived of acquiring factual knowledge.
You will have heard the words “fact,” “hypothesis,” and “theory” used constantly in the conduct of scientific research. When separated from experience and spoken of as abstract ideas they are easily misunderstood and misapplied. Only in case histories of research, by others and soon by you, will their full meaning become clear.
I’ll give you an example of my own to show you what I mean. I started with a simple observation: ants remove their dead from the nests. Those of some species just dump the corpses at random outside, while those of other species place them on piles of refuse that might be called “cemeteries.” The problem I saw in this behavior was simple but interesting: How does an ant know when another ant is dead? It was obvious to me that the recognition was not by sight. Ants recognize a corpse even in the complete darkness of the underground nest chambers. Furthermore, when the body is fresh and in a lighted area, and even when it is lying on its back with its legs in the air, others ignore it. Only after a day or two of decomposition does a body become a corpse to another ant. I guessed (made a hypothesis) that the undertaker ants were using the odor of decomposition to recognize death. I further thought it likely (second hypothesis) that their response was triggered by only a few of the substances exuded from the body of the corpse. The inspiration for the second hypothesis was an established principle of evolution: animals with small brains, which are the vast majority of animals on Earth, tend to use the simplest set of available cues to guide them through life. A dead body offers dozens or hundreds of chemical cues from which to choose. Human beings can sort out these components. But ants, with brains one-millionth the size of our own, cannot.
So if the hypotheses are true, which of these substances might trigger the undertaker response—all of them, a few of them, or none? From chemical suppliers I obtained pure synthetic samples of various decomposition substances, including skatole, the essence of feces; trimethylamine, the dominant odor of rotting fish; and various fatty acids and their esters of a kind found in dead insects. For a while my laboratory smelled like a combination of charnel house and sewer. I put minute amounts on dummy ant corpses made of paper and inserted them into ant colonies. After a lot of smelly trial and error I found that oleic acid and one of its oleates trigger the response. The other substances were either ignored or caused alarm.
To repeat the experiment another way (and admittedly for my and others’ amusement), I dabbed tiny amounts of oleic acid on the bodies of living worker ants. Would they become the living dead? Sure enough, they did become zombies, at least broadly defined. They were picked up by nestmates, their legs kicking, carried to the cemetery, and dumped. After they had cleaned themselves awhile, they were permitted to rejoin the colony.
I then came up with another idea: insects of all kinds that scavenge for a living, such as blowflies and scarab beetles, find their way to dead animals or dung by homing in on the scent. And they do so by using a very small number of the decomposition chemicals present. A generalization of this kind, widely applied, with at least a few facts here and there and some logical reasoning behind it, is a theory. Many more experiments, applied to other species, would be required to turn it into what can be confidently called a fact.
What, then, in broadest terms is the scientific method? The method starts with the discovery of a phenomenon, such as a mysterious ant behavior, or a previously unknown class of organic compounds, or a newly discovered genus of plants, or a mysterious water current in the ocean’s abyss. The scientist asks: What is the full nature of this phenomenon? What are its causes, its origin, its consequence? Each of these queries poses a problem within the ambit of science. How do scientists proceed to find solutions? Always there are clues, and opinions are quickly formed from them concerning the solutions. These opinions, or just logical guesses as they often are, are the hypotheses. It is wise at the outset to figure out as many different solutions as seem possible, then test the whole, either one at a time or in bunches, eliminating all but one. This is called the method of multiple competing hypotheses. If something like this analysis is not followed—and, frankly, it often is not—individual scientists tend to fixate on one alternative or another, especially if they authored it. After all, scientists are human.
Only rarely does an initial investigation result in a clear delineation of all possible competing hypotheses. This is especially the case in biology, in which multiple factors are the rule. Some factors remain undiscovered, and those that have been discovered commonly overlap and interact with one another and with forces in the environment in ways difficult to detect and measure. The classic example in medicine is cancer. The classic example in ecology is the stabilization of ecosystems.
So scientists shuffle along as best they can, intuiting, guessing, tinkering, gaining more information along the way. They persist until solid explanations can be put together and a consensus emerges, sometimes quickly but at other times only after a long period.
When a phenomenon displays invariable properties under clearly defined conditions, then and only then can a scientific explanation be declared to be a scientific fact. The recognition that hydrogen is one of the elements, incapable of being divided into other substances, is a fact. That an excess of mercury in the diet causes one disease or another can, after enough clinical studies are conducted, be declared a fact. It may be widely believed that mercury causes an entire class of similar maladies, due to the one or two known chemical reactions in cells of the body. This idea may or may not be confirmed by further studies on diseases believed affected in this manner by mercury. Meanwhile, however, when research is still incomplete, the idea is a theory. If the theory is proved wrong, it was not necessarily also altogether a bad theory. At least it will have stimulated new research, which adds to knowledge. That is why many theories, even if they fail, are said to be “heuristic”—they are good for the promotion of discovery. Incidentally, the source of the word eureka—“I have found it!”—descends from the legend of the Greek scientist Archimedes, who, while sitting in a public bath, imagined how to measure the density of an object regardless of its shape. Put it in water, measure its volume by the rise in the water level, and its weight by how fast it sinks in the water. The density is the amount of weight divided by the amount of volume. Archimedes is said to have then left the bath, running through the streets, hopefully in his robe, while shouting, Heurika! Specifically, he’d found how to determine whether a crown was pure gold. The pure substance has a higher density than gold mixed with silver, the lesser of the two noble metals. But of far greater importance, Archimedes had discovered how to measure the density of all solids regardless of their shape or composition.
Now consider a much grander example of the scientific method. It has been commonly said, all the way back to the publication of Charles Darwin’s On the Origin of Species in 1859, that the evolution of living forms is just a theory, not a fact. What could have been said already from evidence in Darwin’s time, however, was that evolution is a fact, that it has occurred in at least some kinds of organisms some of the time. Today the evidence for evolution has been so convincingly documented in so many kinds of plants, fungi, animals, and microorganisms, and in such a great array of their hereditary traits, coming from every discipline of biology, all interlocking in their explanations and with no exception yet discovered, that evolution can be called confi
dently a fact. In Darwin’s time, the idea that the human species descended from early primate ancestors was a hypothesis. With massive fossil and genetic evidence behind it, that can now also be called a fact. What remains a theory still is that evolution occurs universally by natural selection, the differential survival and successful reproduction of some combinations of hereditary traits over others in breeding populations. This proposition has been tested so many times and in so many ways, it also is now close to deserved recognition as an established fact. Its implication has been and remains of enormous importance throughout biology.
When a well-defined and precisely consistent process is observed, such as ions flowing in a magnetic field, a body moving in airless space, and the volume of a gas changing with temperature, the behavior can be precisely measured and mathematically defined as a law. Laws are more confidently sought in physics and chemistry, where they can be most easily extended and deepened by mathematical reasoning. Does biology also have laws?
I have been so bold in recent years as to suggest that, yes, biology is ruled by two laws. The first is that all entities and processes of life are obedient to the laws of physics and chemistry. Although biologists themselves seldom speak of the connection, at least in such a manner, those working at the level of the molecule and the cell assume it to be true. No scientist of my acquaintance believes it worthwhile to search for what used to be called the élan vital, a physical force or energy unique to living organisms.
Letters to a Young Scientist Page 3